Quaternary ammonium compounds can be synthesized from their perspective tertiary amines by alkylation. However, the synthesis of quaternary ammonium compounds often results in low yield due to incomplete reactions and unwanted side reactions. The presence of unreacted tertiary amines or side products can make purification difficult. Side reactions include Hofmann elimination and rearrangement reactions. Quaternary ammonium salts react readily under transfer of alkyl groups or under Hofmann elimination under basic conditions. Frequently, both reactions are observed in parallel. (U.S. Pat. No. 6,166,232).
Opiates are a class of compounds in which many of the compounds contain a tertiary nitrogen that can be quaternized to modulate their mode of action. Opiates have been the subject of intense research since the isolation of morphine in 1805, and thousands of compounds having opiate or opiate-like activity have been identified. Among the well known quaternized morphinan compounds is methyl naltrexone (RELISTOR®) used for reducing some of the side effects of opiate drugs. (Goldberg et al., U.S. Pat. No. 4,176,186; Dlubala A, U.S. Pat. No. 7,645,880).
Morphinans are known to undergo ring Hofmann elimination and ring opening to result in tricyclic compounds under base catalyzed quaternization process. (Arrington et al., Bioorganic & Medicinal Chemistry Letters 14 (2004) 1807-1809). Anastasia et al., reports ring opening.